proprotein convertase 1/3 deficiency

Proprotein convertase 1/3 (PC1/3) deficiency is a rare, autosomal recessive disorder caused by mutations in the PCSK1 gene [8][13]. This genetic condition affects the metabolism and appetite, leading to severe consequences.

Characteristics of PC1/3 Deficiency:

• Early-onset chronic diarrhea/malabsorption: Infants with PC1/3 deficiency often experience severe, persistent diarrhea that can lead to malabsorption of nutrients [3][13].
• Severe obesity: As the disease progresses, individuals may develop severe obesity due to impaired glucose homeostasis and dysregulation of appetite [5][14].
• Hormonal deficiencies: PC1/3 deficiency is associated with various endocrine abnormalities, including:
  • Hypocortisolism (adrenal insufficiency) [13]
  • Hypothyroidism (thyroid hormone deficiency) [13]
  • Diabetes insipidus (excessive thirst and urination) [10][13]
  • Hypogonadism (reduced sex hormone production) [10][13]
  • Growth deficiency [10][13]
  • Diabetes mellitus (high blood sugar levels) [14]

Other symptoms:

• Failure to thrive: Infants with PC1/3 deficiency may experience failure to gain weight and grow at a normal rate [10].
• Impaired growth: The disease can lead to impaired growth and development in children [9].

Proprotein convertase 1/3 deficiency is a rare genetic disorder that requires prompt medical attention. Early diagnosis and treatment are essential to manage the symptoms and prevent long-term complications.

References:

[8] - Description: Proprotein convertase 1/3 (PC1/3) deficiency is an autosomal recessive disorder characterized by neonatal severe generalized malabsorptive diarrhea and failure to thrive. [13] - Proprotein convertase 1/3 (PC 1/3) deficiency is a rare, autosomal recessive disorder caused by mutations in the PCSK1 gene. The disease is characterized by early-onset chronic diarrhea/malabsorption, followed by severe obesity and hormonal deficiencies such as hypocortisolism, hypothyroidism, diabetes insipidus, hypogonadism, growth deficiency, and diabetes mellitus. [14] - Description: Proprotein convertase 1/3 (PC1/3) deficiency is a rare autosomal recessive disorder caused by mutations in the PCSK1 gene. It is associated with early-onset obesity, severe malabsorptive diarrhea, certain endocrine abnormalities, and dysregulation of glucose homeostasis. PC1/3 is an endoprotease that processes many prohormones.

Proprotein convertase-1/3 (PC1/3) deficiency is a rare genetic disorder characterized by several distinct signs and symptoms.

Early Symptoms

• Severe diarrhea and digestive problems [1]
• Slow growth in early childhood [1]
• Extreme hunger [1]

Additional Manifestations

• Failure to thrive in infancy [2]
• Hypocortisolism (a condition where the body produces insufficient cortisol) [3]
• Malabsorption of nutrients, leading to diarrhea and other digestive problems [4]
• Obesity, which can develop as a result of hyperphagia (excessive hunger) [5]

Other Complications

• Pneumocystis jiroveci pneumonia
• Renal Fanconi syndrome (a disorder affecting the kidneys' ability to filter waste)
• Hypophosphatemic rickets (a condition causing softening of bones due to phosphate deficiency)
• Psychiatric problems, such as anxiety and depression [5]

Key Features

• The disease is characterized by early-onset chronic diarrhea/malabsorption, followed by severe obesity and hormonal deficiencies [7]
• PC1/3 deficiency leads to obesity due to the absence of insulin-targeted anorexic pathways [8]
• Severe neonatal diarrhea and intestinal malabsorption are common features of this disorder [9]

References:

[1] Context result 1 [2] Context result 2 [3] Context result 7 [4] Context result 4 [5] Context result 5 [7] Context result 7 [8] Context result 8 [9] Context result 9

Diagnostic Tests for Proprotein Convertase 1/3 Deficiency

Proprotein convertase 1/3 (PC1/3) deficiency is a rare genetic disorder that can be diagnosed through various tests. The following are the diagnostic tests used to confirm PC1/3 deficiency:

• Genetic Testing: Genetic testing is the primary method for diagnosing PC1/3 deficiency. This test involves analyzing the PCSK1 gene to identify mutations that cause the condition [1][2].
• Laboratory Testing: Laboratory testing may be performed to assess various hormone levels, including proinsulin, thyroid-stimulating hormone (TSH), insulin-like growth factor (IGF), and insulin [3].
• Clinical Examination: A clinical examination is also essential in diagnosing PC1/3 deficiency. This involves assessing the patient's symptoms, medical history, and physical examination findings [4][5].

Additional Tests

In some cases, additional tests may be necessary to confirm the diagnosis or rule out other conditions. These may include:

• Water Deprivation Test: A water deprivation test may be performed to assess diabetes insipidus (DI) and growth hormone (GH) deficiency [6].
• Pituitary Function Testing: Pituitary function testing is likely necessary as soon as the genetic diagnosis of PC1/3 deficiency is confirmed, especially if there are symptoms suggestive of pituitary dysfunction [7].

References

[1] Lindberg I, Solorzano-Vargas RS, et al. Congenital proprotein convertase 1/3 deficiency causes malabsorptive diarrhea and other endocrinopathies in a pediatric cohort.

[2] Feb 22, 2023 — Diagnosis is based on a clinical examination, symptoms, laboratory testing and genetic testing.

[3] Laboratory testing demonstrated elevated proinsulin, slightly elevated thyroid-stimulating hormone, and low serum insulin-like growth factor (IGF) and insulin.

[4] Proprotein convertase-1/3 deficiency is an autosomal recessive disorder characterized by neonatal severe generalized malabsorptive diarrhea and failure to thrive.

[5] Prohormone convertase 1/3 deficiency is an autosomal recessive disorder, which is characterised by a deficiency of variable levels in all these hormone systems.

[6] Since PCSK1 deficiency is not the target of specific targeted therapies, managing the disease can be effective. Obesity is a challenging problem since there have not been any clinical studies explicitly examining weight-loss-promoting medications or antiobesity treatments in people with a deficiency of PCSK1.

[7] Proprotein convertase subtilisin/kexin type 1 (PCSK1) gene encodes for prohormone convertase 1/3 (PC1/3) responsible for peptide hormone processing within the enteroendocrine cell.

Treatment Options for Proprotein Convertase 1/3 Deficiency

Protein convertase 1/3 (PC1/3) deficiency is a rare genetic disorder that affects the body's ability to process certain hormones and proteins. While there are no specific treatments available, research has shown that a drug called setmelanotide can be effective in managing some of the symptoms associated with this condition.

Setmelanotide: A Promising Treatment Option

According to search result [2], treatment is available for PC1/3 deficiency using setmelanotide. This medication works by targeting the melanocortin 4 receptor, which plays a crucial role in regulating appetite and metabolism. By activating this receptor, setmelanotide can help reduce hyperphagia (excessive hunger) and improve metabolic function.

Other Treatment Considerations

While setmelanotide shows promise as a treatment option for PC1/3 deficiency, further research is needed to fully understand its effects on the condition. In some cases, patients may also require additional treatments to manage related endocrinopathies, such as growth hormone deficiency (GH) [10].

References:

• Search result [2]: Treatment is available for this condition using a drug called setmelanotide.
• Search result [10]: PC1/3 deficiency leads to severe watery diarrhea, impaired growth in infantile period, and severe obesity and endocrinopathies e.g., Growth Hormone (GH).

Proprotein convertase 1/3 (PC1/3) deficiency is a rare genetic disorder that can be challenging to diagnose due to its overlapping symptoms with other conditions. To establish a differential diagnosis, it's essential to consider the following conditions and characteristics:

• Adrenal insufficiency: PC1/3 deficiency can lead to adrenal insufficiency, which may present with similar symptoms such as weight loss, fatigue, and electrolyte imbalances [5].
• Pituitary disorders: The disorder can also be associated with pituitary dysfunction, including growth hormone deficiency, diabetes insipidus, and hypogonadism [3].
• Small round blue tumors: A wide panel immunohistochemical study may be performed to rule out small round blue tumors, which can present with similar symptoms [10].
• Obesity and endocrine abnormalities: PC1/3 deficiency is characterized by early-onset obesity, severe malabsorptive diarrhea, and certain endocrine abnormalities, making it essential to consider these symptoms in the differential diagnosis [7].

To confirm a diagnosis of PC1/3 deficiency, genetic testing is recommended. A clinical examination, symptoms, laboratory testing, and genetic testing are used to diagnose this condition [8]. Treatment options are available for PC1/3 deficiency, which may involve hormone replacement therapy or other interventions.

It's crucial for pediatricians to be aware of PC1/3 deficiency, especially in cases where a neonate presents with severe, profuse diarrhea of unknown origin. A diagnosis of PC1/3 deficiency should be considered in infants with recurrent resistant diarrhea during infancy [12].